HHS adds H5N1 clade 2.2 vaccine to stockpile

Apr 29, 2008 (CIDRAP News) – The US Department of Health and Human Services (HHS) has accepted the first batch of H5N1 avian influenza vaccine based on the H5N1 variant known as clade 2.2, which has spread most widely across Asia, Europe, and Africa.

Sanofi Pasteur announced yesterday that HHS is paying $192.5 million for the vaccine, which is being shipped in bulk form. The number of doses it represents will depend on the final formulation of the vaccine, but the amount could be used to make from 6.4 million to 38.5 million doses or more, the company said.

"This acceptance represents the US government's latest effort to diversify the vaccine stockpile program to include new strains of the H5N1 virus," Sanofi said in a news release. The vaccine is based on H5N1 clade 2.2, the variant that caused the outbreak in bar-headed geese and other birds at China's Quinghai Lake in 2005, the statement said. It was made at Sanofi's plant in Swiftwater, Pa.

Clade 2.2 viruses have sparked outbreaks in more than 60 countries in Africa, Asia, and Europe, with human cases in Azerbaijan, China, Djibouti, Egypt, Iraq, Nigeria, Pakistan, and Turkey, the World Health Organization reported in February.

US officials hope that existing H5N1 vaccines will provide some protection for critical personnel in the early stages of a pandemic, should the H5N1 virus evolve into a pandemic strain. In a pandemic, it is expected to take several months to develop and start producing a vaccine closely matched to the new strain.

Robin Robinson, PhD, director of HHS's Biomedical Advanced Research and Development Agency (BARDA), confirmed that the supply received from Sanofi represents the first clade 2.2 vaccine to be added to the Strategic National Stockpile.

Sanofi called the strain "particularly troubling because it is the first to be identified in an outbreak of migratory birds, which have the potential to spread the virus across continents."

Robinson told CIDRAP News the national stockpile already contains supplies of vaccine based on three other H5N1 variants: clade 1, clade 2.1, and clade 2.3. HHS has sought to diversify the stockpile out of concern that a vaccine based on one strain won't work well against a pandemic virus stemming from a different strain.

The stockpile was begun with a Sanofi vaccine based on a clade 1 virus from Vietnam, he said. In 2006 and 2007 HHS purchased vaccines based on clade 2.1, a strain identified in Indonesia, from Sanofi, GlaxoSmithKline (GSK), and Novartis, he reported. In addition, he said the agency has bought some vaccine from Novartis that's based on clade 2.3, a strain from Anhui province in China.

Robinson said the stockpile currently contains enough H5N1 vaccine to cover about 12 million to 13 million people, assuming two 90-microgram (mcg) doses per person. The vaccines are stored in bulk form, and it may be possible to use smaller doses if various trials of the vaccines with adjuvants (immune-boosting chemicals) are successful, he said.

"This fall we should hit our goal [of having enough vaccine] for 20 million people," Robinson said. "If the adjuvants become a reality we'll be able to have more than that." He reported that Sanofi vaccines make up about two thirds of the stockpile, while the GSK and Novartis vaccines account for about 17% each.

Sanofi's announcement yesterday said the clade 2.2 vaccine supplied to HHS would be good for 6.4 million 90-mcg doses. But if the amount could be reduced to 15 mcg per dose—the amount for each strain in seasonal flu vaccines—the supply would amount to 38.5 million doses.

"If we had a really successful adjuvant, it could be even much higher than the numbers in the press release," Sanofi spokesman Len Lavenda told CIDRAP News. He said the company is working on adjuvants.

Robinson said HHS is supporting the development of adjuvants by GSK, Novartis, and Iomai Inc. Iomai's adjuvant is delivered by a skin patch rather than by being mixed with the vaccine antigen and injected.

The GSK and Novartis adjuvants for H5N1 vaccine "are in a very advanced stage of development in that they are hopefully going to submit licensure applications to the FDA [Food and Drug Administration] later this year," Robinson said. He noted that the adjuvants are not licensed as separate products, but only in combination with a vaccine. If the adjuvanted vaccines are licensed, HHS can consider adding them to the national stockpile, he said.

Robinson also said there are plans for a "mix and match" clinical trial in which Sanofi's vaccine antigen will be combined with adjuvants from GSK and Novartis. The aim will be to see if the adjuvanted vaccines are safe and if they produce immune responses similar to those of the corresponding GSK and Novartis vaccines, he said.

In addition, under an HHS contract, Sanofi will be testing split-virus and whole-virus H5N1 vaccines with two other adjuvants, involving aluminum hydroxide and an oil-and-water emulsion, Robinson said.